Process for the preparation of bromochlorofluoroethanes



United States Patent O" PROCESS FOR THE PREPARATION OFBROMOCHLOROFLUOROETHANES James Chapman and Robert Leslie McGinty,Widnes,

' England, assignors to Imperial Chemical Industries krmited, London,England, a corporation of Great ritain No Drawing. Application February25, 1957 Serial N0. 641,825

Claims priority, application Great Britain February 29, 1956 9 Claims.(Cl. 260-6533) This invention provides a novel method for thepreparation of the halohydrocarbons lllll-tl'lfillOlO-Z-bl'OlIlOr2-chloroethane and 1 l-difluoro-l :2-dichloro-2-bromoethane, of theformulae CF -CHBrCl and CF CLCHBICI respectively, which are useful asinhalation anaesthetics. There have been described in copendingapplication U.S. Serial No. 539,689, filed October 10, 1955, now US.Patent No. 2,849,502, two alternative methods for the preparation of1:1:l-trifluoro-2-bromo-2-chloroethane by a three-stage synthesis,starting from trichloroethylene. We have now found that it can beobtained by a two-stage process, namely by the fiuorination of1:2-dibromo- 1:1:2-trichloroethane, which itself is obtainable by directbromination of trichloroethylene. The course of this fluorination istotally unexpected having regard to statements in the literatureconcerning the fluorination of ethane derivatives.

Henne and his collaborators have carried out an extensive programme ofwork on fluorinationreactions and the results of these studies have beencritically reviewed by others, who have sought to deduce therefrom aseries of systematic general conclusions and to devise rules that couldbe used as a basis for predicting the course of other fiuorinationreactions. Thus Sidgwick, at page 1121 of volume 11 of his book TheChemical Elements and their Compounds (Oxford University Press, 1950),and Stacey in an article on Organic Fluorine Compounds in Progress inOrganic Chemistry, volume 2, edited by J. W. Cooke (Butterworth 1953) atpage 62, both put forward observations regarding the mechanism offluorination. From the statements of these authors, and the practicalresults reported in the literature it is apparent that the followingstatements are generally accepted by workers in the field of fluorinechemistry, namely that:

(1'). The replacement by fluorine of another halogen is very diflicultwhen there are not at least two halogen atoms on the carbon in question.

2) Fluorination is easier with the C(halogen) group than withCH(halogen) provided the halogens in question are not fluorine. But thepresence of a fluorine atom on a carbon makes other halogen atoms onthat carbon diflicult to replace and the presence of two fluorines makesthe replacement much more difficult particularly where the adjacentcarbon atom has at least two halogen atoms on it.

A demonstration of the above conclusions is the fluorination of CHC1.CCl which first gives CHCl .CCl F and then CHCl CClF At this pointfurther replacement on the first carbon is difficult owing to thepresence of hydrogen, and on the second due to the protective effect ofthe two fluorine atoms; but it is possible with difliculty to getCHClFCClF and then CHF CClF According to the above conclusions one wouldexpect 2,921,099 Patented Jan. 12, 1960 ice that the fluorination of CClBrCHClBr would proceed as follows:

coaster-toner CClF CHClBr CC1F CHClF get replacement in the -CH(halogen)group, hence.

one would expect to obtain CClF CHClF. At this stage furtherfluorination on either, carbon is difficult, and unless very drasticconditions were used one would not expect any further replacement.

We have found however that when 1:2-dibromo-1 1:2- trichloroethane isfluorinated with HF and an antimony fluochloride catalyst, then,presumably following the expected conversion to2-bromo-1z2-dichloro-1:l-difluoroethane, there is formed, surprisingly,a substantial proportion of an unexpected product, namely, 2-bromo-2-chloro-1:1:l-trifluoroethane; that is, the -C(halogen) group has all thehalogens replaced by fluorine and none of the halogens in theCH(halogen) group are replaced. While this has been done with compoundshaving a C(halogen) -CH .halogen structure, such as CCl .CH Cl and CBrCl.CH Br, which gives CF CH Cl and CF CH Br respectively, in the light ofthe conclusions reached by Sidgwick and by Stacey such a reaction isunexpected with a C(hal0gen) -CH(halogen) structure. We can thus mostunexpectedly make 2bromo-2- chloro-1:1:l-trifiuoroethane byfluorination, by means of HF and an antimony fluochloride catalyst,either of 1:2- dibromo-l:1:2-trichloroethane or of the intermediateproduct, 2-bromo-1:2-dichloro-1: l-difiuoroethane.

The said intermediate conversion product, 2-bromo-1z2-dichloro-lzl-difluoroethane, a proportion of which also appears in thereaction product, is itself a new compound which has properties thatmake it of interest as a nontoxic, non-explosive inhalation anaesthetic.

Either or both of these products, or, if desired, a mixture of the two,can readily be separated from the reaction product by conventionalmeans, for example, by fractional distillation.

Our invention therefore provides a process for the manufacture of2-bromo-2-chloro-1: 1 l-trifluoroethane or2-bromo-1z2-dichloro-1:l-difluoroethane or a mixture of these compoundswhich comprises heating 1:2-dibromolzl'z2-trichloroethane withsubstantially anhydrous hyd'rogen fluoride at a temperature in the range-200 C. and in the presence of an antimony fluorochloride catalystcontaining at least 20% of pentavalent antimony and separating from thereaction product the desired compound or mixture of compounds.

It also provides an alternative process of making 2- bromo 2 chloro1:1:1 trifluoroethane by fluorinating under the same conditions thealternative starting material 2-bromo-lz2-dichloro-1:l-difluoroethaneand as before separating the requiredproduct from the reaction mixture.

The reaction is preferably carried out under pressure, primarily so asto keep the reactants liquid in the reaction vessel, and secondly toexert some control on the temperature of the reaction. The reaction maybe carried out satisfactorily at temperatures in the range 90200 C.preferably 140 C. The materials produced by the reaction are primarily2-br0rno-2-chl0ro-1:1:1-t1ifluoroethane and 2-bromo-1 :2-dichloro-11-difluorothane with accompanying by-products. The relative proportionsof the two named products and the proportions and nature of theby-products are affected by the proportions of the reactants and, to aminor extent, of the catalyst,

3 the reaction temperature and the catalyst composition, but the2-bromo-2-chloro-1:lzl-trifluoroethane and 2-bromo-lzZ-dichloro-l:l-difluoroethane may be separated from the reactionmixture and from each other by conventionalmethods, such as fractionaldistillation.

By the term antimony fluochloride catalyst as used above, we mean todenote a catalyst which is a mixture of antimony fluorides andchlorides, some part of which contains antimony in the pentavalentstate. Such a catalyst can be conveniently made in situ by introducinginto the reaction vessel hydrogen fluoride together with antimonypentachloride or a mixture in appropriate proportions of antimonytrichloride and antimony pentachloride and heating them to bring aboutreaction; during this reaction the chlorides are in part converted, asis known, into the fluorides, with elimination of hydrogen chloride. Theactivity of the catalyst is primarily governed by its fluorine contentand the proportion of pentavalent antimony present.

. The composition of the catalyst may be varied between quite widelimits provided, however, that it contains a sufficient proportion ofpentavalent antimony. We have found that the proportion of pentavalentantimony present in the catalyst to the total antimony present thereinshould be at least 20% and preferably at least 50%. A fully pentavalentcatalyst gives good conversions of 1 :Z-dibromo-l 1 :2-trichloroethaneto 2-bromo-2-chlorolzlzl-trifluoroethane; a lower degree of pentavalencytends to give greater proportions of Z-bromo-l:2-dicholrolzl-difluoroethane. However, with a highly pentavalentcatalyst the proportion of accompanying by-products is increased. Thusthe choice of catalyst composition and the correlation of thatcompositionwith the other variables in the reaction is mainlyconditioned by the relative proportions of the main products desired andthe extent to which it is important to minimize the formation ofby-products. For instance, where a preponderance of2-bromo-2-chloro-l:lzl-trifluoroethane is desired and eflicientseparation devices are available, the more efficient conversionsachieved by a fully pentavalent catalyst can be utilized, this advantagebeing offset by the necessity to carry out a slightly more diflicultseparation of the desired 2-bromo-2-chloro-1:1:l-trifiuoroethane. workwith a less pentavalent catalyst and obtain a mixture of products fromwhich 2-bromo-2-chloro-1z1:l-trifluoroethane is more readily separable.The particular conditions to be used in any given case will be governedlargely by economic factors but as long as the catalyst contains atleast 20% of pentavalent antimony and the temperature is within therange described, both 2-bromo- 2-chloro-1: 1 l-trifluoroethane and2-bromo-1 :2-dichlorolzl-difluoroethane will be formed and either orboth or a mixture of the two may be separated from the reaction productsat will.

High temperature and an active catalyst favor the more completefluorination, lower temperature and a less active catalyst increase theproportion of 2-bromo-1z2-dichlorolzl-difluoroethane. Too high atemperature and/or too active a catalyst will lead to the formation ofunwanted by-products.

.The two main products are readily separated from one another byfractional distillation.

, The following examples illustrate but do not limit the invention: theparts are by weight.

Example I In other circumstances it may be desirable to in. gauge. 2037parts of l:Z-dibromo-l:1:2-trichloroethane and 500 parts of hydrogenfluoride were then added to the autoclave. The temperature was raised to120 to 140 C. for 3% hours, the pressure being maintained in the range400 to 450 pounds per sq. in. gauge. At the end of this period, thevessel was cooled to atmospheric temperature and the remaining pressurereleased. The contents were then distilled, 344 parts of materialboiling at 50 to 52 C. and 545 parts boiling at 94 to 96 C. wereobtained. The identity of the fraction boiling at 50 to 52 C. wasestablished in the following manner.

Analysis gave the following figures: C=12.2%, F=29.0%, Cl=l8.0%,Br=40.5%. Molecular weight =190. C HF ClBr requires: C=l2.l%, F=28.9%,Cl=l8.0%, Br=40.4%. Molecular weight=l97.5.

Its identity with 2-bromo-2-chloro-lz1:l-trifluoroethane was shown byexamination of the following physical properties, boiling point(B.P.=50.2 C./760 mm.) refractive index (1.3700 at 20 C.) and by thefact that on treatment with zinc dust and ethanol it gave2-chlorolzlzl-trifluoroethane, as does the authentic 2-bromo-2-chloro-l:lzl-trifiuoroethane made by the process of U.S. Patent No.2,849,502. Further confirmation was obtained by showing that a sampleprepared by the method of the present application was indistinguishableby mass spectrometry and vapor phase chromatography from a sampleprepared by the method of U.S. Patent No. 2,849,502.

The identity of the fraction boiling at 94 to 96 C. was determined inthe following manner:

Analysis gave the following figures: C=1l.3%, Br=37.3%, Cl=33.1%,F=17.7%. Molecular weight =220. C HF CIBr requires: C=11.2%, Br=37.4%,

Cl=33.1%, F=l7.8%. Molecular weight=2l4.

The boiling point was found to be 95.5 C./760 mm. and the refractiveindex at 20 C. was 1.4298. Chemical degradation confirmed that thecompound was 2- bromo-l :2-dichloro-l l-difluoroethane.

The 1:2-dibromo-1:1:2-trichloroethane used as starting material in thisexample was conveniently prepared by treating trichloroethylene withbromine at 30 to 40 C. with light activation.

Example II Another run was carried out in a similar manner to Example I,the proportion of pentavalent antimony in the catalyst being variedslightly. The proportions of the materials used in preparing thecatalyst were 2 moles of antimony trichloride, 3 moles of antimonypentachloride and 15 moles of hydrogen fluoride. When the catalyst hadbeen prepared in the same manner as Example I, 15 moles of1:2-dibromo-l:l:2-trichloroethane and 20 moles of hydrogen fluoride wereadded to the autoclave. The temperature was raised to 107 to 130 C. for3 hours and the pressure maintained in the range 400 to 450 pounds persq. in. gauge. At the end of this period, the vessel was cooled toatmospheric temperature and the pressure released. The contents werethen fractionally distilled, the yield of2-bromo-2-chlorolzlzl-trifluoroethane separated by the distillation was29.7%. A yield of 22% of 2-bromo-1:2-dichloro-1:1- difluoroethane wasalso obtained.

Example III Another example of the process of the invention is thecarrying out of the reaction using a fully pentavalent catalyst. 9 molesof antimony pentachloride and 36 moles of hydrogen fluoride were heatedin a mild steel autoclave at to C. for one hour. The hydrogen chlorideevolved was released through a reflux condenser which was also withinthe pressure system and cooled with solid carbon dioxide andtrichloroethylene, atv such a rate that the pressure was maintained at200 pounds per sq. in. gauge. 6 moles of 1:2-dibromople.

1:1:2-trichloroethane and 26 moles of hydrogen fluoride were then addedto the autoclave. The temperature was raised to 90 to 120 C. for hours,the pressure being maintained at 250 pounds per sq. in. gauge. of thisperiod, the vessel was cooled to atmospheric temperature and theremaining pressure released. From the contents of the autoclave, anamount of 2-bromo-2- chloro-l:1:1-trifiuoroethane equivalent to a yieldof 39% was separated by fractional distillation. The yield of2-bromo-lz2 dichloro-l:l-difluoroethane in this case was Example IVAnother example of the process of the invention is the furtherfluorination of 2-bromo-1:2dichloro-1:1-difluoroethane to2-bromo-2-chloro-l 1 l-trifluoroethane, which was carried out asfollows.

4 moles of antimony trichloride, 4 moles of antimony pentachloride and24 moles of hydrogen fluoride were heated in a mild steel autoclave at90 to 100 C. for 1 hour maintaining the pressure at 200 pounds per sq.in. gauge in the manner described in the previous exam- 5 moles of2-bromo-1z2-dichloro-1: l-difluoroethane and 7% moles of hydrogenfluoride were then added to the autoclave and the temperature was raisedto 90 to 120 C. for 3 /2 hours. At the end of this period the vessel wascooled to atmospheric temperature and the pressure released. Thecontents were then fractionally distilled. Both 2-bromo-2-chloro-1: 1:l-trifluoroethane and some unchanged2-bromo-1:2-dich1oro-1:1difluoroethane were obtained. The yield of2-bromo-2-chlorolzlzl-trifluoroethane was 42% calculated on the organicreactant consumed.

What we claim is:

1. A process for the manufacture of 2-bromo-2-chloro-1:1:1-trifluoroethane which comprises heating Z-bromo-1:2-dichloro-1:1-difluoroethane with substantially anhydrous hydrogenfluoride at a temperature in the range 90 to 200 C. and in the presenceof an antimony fluochloride catalyst containing at leas 20% ofpentavalent antimony and separating the resultant2-bromo-2-chlorolzlzl-trifiuoroethane from the reaction product.

2. A process for the manufacture of a member selected from the groupconsisting of 2-bromo-2-chlorolzlzl-trifluoroethane and 2-bromo-l:2-dichloro-1:l-difiuoroethane and mixtures thereof whchcomprises heating 1:2-dibromo-1:1:2-trichloroethane with substantiallyanhydrous hydrogen fluoride at a temperature in the range 90 to 200 C.and in the presence of an antimony fluochloride catalyst containing atleast 20% of pentavalent antimony, and separating the desiredsaid'member from the reaction product.

At the end 3. A process according to claim 2, wherein the catalystcontains at least 50% of pentavalent antimony.

4. A process according to claim 2 wherein the reaction is carried out'ata temperature in the range -140 C.

5. A process according to claim 2 wherein the reaction is carried out ata pressure greater than atmospheric.

6. Process for the manufacture of a mixture of 2- bromo-2-ch1oro-1 1l-trifiuoroethane and 2-bromo-1 :2- dichloro-l:I-difluoroethane whichcomprises heating 1:2- dibromo-l:1:2-trichloroethane with substantiallyanhydrous hydrogen fluoride at a temperature from to 140 C. in thepresence of antimony fluochloride catalyst containing at least 20% ofpentavalent antimony.

7. Process for the manufacture of a mixture of 2- bromo-2-chloro-1 1l-trifluoroethane and 2-bromo-1z2- dichloro-l:l-difluoroethane whichcomprises heating 1:2- dibromo-l:1:2-trichloroethane with substantiallyanhydrous hydrogen fluoride at a temperature from 107 to C. in thepresence of antimony fluochloride catalyst containing at least 20% ofpentavalent antimony.

8. A process for the manufacture of a product consisting essentially of2-bromo-2-chloro-1:lzl-trifluoroethane which comprises heating2-bromo-1:2-dichlorolzl-difluoroethane with substantially anhydrousfluoride at a temperature from 90 C. to 120 C. in the presence of fullypentavalent antimony fluochloride and separating said product from thereaction mixture.

9. A process for the production of 2-bromo-2-chlorolzlzl-trifiuoroethanewhich comprises heating 2-bromo- 1:2-dichloro-1:l-difiuoroethane withsubstantially anhydrous hydrogen fluoride at a temperature from 90 C. to120 C. in the presence of antimony fluochloride catalyst containing atleast 20% pentavalent antimony.

References Cited in the file of this patent UNITED STATES PATENTS1,930,129 Midgely et al. Oct. 10, 1933 2,146,354 Scherer Feb. 7, 19392,230,925 Benning Feb. 4, 1941 2,500,218 Towne et a1. Mar. 14, 19502,644,845 McBee July 7, 1953 2,724,004 Frederick Nov. 15, 1955 2,849,502Suckling et al. Aug. 26, 1958 OTHER REFERENCES Henne et al.: Jour. Am.Chem. Soc., vol. 58, pages 402-403, March 1936.

Park et al.: Jour. Am. Chem. Soc., vol. 71, pages 2339-2340, July 1949.

2. A PROCESS FOR THE MANUFACTURE OF A MEMBER SELECTED FROM THE GROUPCONSISTING OF 2-BROMO-2-CHLORO1:1:1-TRIFLUOROETHANE AND2-BROMO-12-DICHLORO-1:1-DIFLUORETHANE AND MIXTURES THEREOF WHICHCOMPRISES HEATING 1:2-DIBROMO-1:1:2-TRICHLOROETHANE WITH SUBSTANIALLYANHYDROUS HYDROGEN FLUORIDE AT A TEMPERATURE IN THE RANGE 90* TO 200* C.AND IN THE PRESENCE OF AN ANTIMONY FLUOCHLORIDE CATALYST CONTAINIG ATLEAST 20% OF PENTAVALENT ANTIMONY, AND SEPARATING THE DESIRED SAIDMEMBER FROM THE REACTION PRODUCT.